Team:Technion Israel/Modeling
3-\(\alpha \)-HSD Kinetic Model
\(\begin{array}{l}\frac{{d\left[ {3 - \alpha - d} \right]}}{{dt}} = \frac{{d{{\left[ {3 - \alpha - d} \right]}_{forward}}}}{{dt}} + \frac{{d{{\left[ {3 - \alpha - d} \right]}_{backward}}}}{{dt}} = \\ = \left[ {3 - \alpha - HSD} \right] \cdot \left( {{K_{ca{t_1}}} \cdot \frac{{\left[ {DHT} \right]}}{{{K_{{m_1}}} + \left[ {DHT} \right]}} - {K_{ca{t_2}}} \cdot \frac{{\left[ {3 - \alpha - d} \right]}}{{{K_{{m_2}}} + \left[ {3 - \alpha - d} \right]}}} \right)\end{array}\)
Background
3-\(\alpha \)-HSD is a name of a group of enzymes which convert certain hormones (like DHT) to another hormone (like 3-α-diol) and vice versa by means of oxidation and reduction. There are several strands of this enzyme, with different level of potency. In humans, the enzyme is encoded by the AKR1C4 gene, while in rat it is encoded by the AKR1C9 gene. We chose the rat version of the enzyme because it is more efficient in breaking down DHT [need article].
All AKRs catalyze an ordered bi-bi reaction in which the cofactor binds first, followed by the binding of the steroid substrate. The steroid product is the first to leave, and the cofactor is the last. In this mechanism, \({K_{cat}}\) represents the slowest step in the kinetic sequence [2].
Approaches to modeling the process
1. Cofactor saturation assumption
We assume that the levels of the cofactors on the scalp are high enough so that they are always saturated in the enzymatic reaction. The advantage of this approach is that we can use the michaelis-menten reversible equation to describe the reaction. As we will explain later, this assumption may not be correct so we will offer other approaches. Another major disadvantage of this model is that it does not take the levels of cofactors into consideration, so it cannot help us to predict the system's behavior for different cofactor concentrations.
2. New Model Development
Taking cofactors into consideration, we can use principles from statistical mechanics in order to develop a completely new enzyme reaction function. The advantage of this approach is that it describes the kinetics of the enzyme in much more detail than michaelis-menten reversible, and can even offer some explanations to our wetlab results. The disadvantage of this approach is that there are no reaction constants available for it, so we will have to estimate them.